Interpretive Summary: Consumption of sweeteners containing fructose has increased dramatically in the American diet over the past 3 decades, in parallel with the increasing incidence of obesity. We studied the effect of consuming large quantities of beverages (about 25% of total calorie intake) sweetened with fructose over a 10 week period in overweight men and women and compared the effects to those produced by an equivalent amount of beverages sweetened with pure glucose. The ingestion of both glucose- and fructose-sweetened beverages led to decreases in metabolic rate. Compared to ingestion of glucose-sweetened beverages, the ingestion of fructose-sweetened beverages with meals caused a greater reduction of the amount of fat burned following the meals. These changes in metabolism, that occurred over a period of 10 weeks, contributed to weight gain. In those subjects consuming fructose-sweetened beverages, the reduction of fat-burning was also associated with an increase of fat deposited in the abdominal area. These findings suggest that consumption of large amounts of sugar, particularly fructose, on a daily basis produces unfavorable changes in energy metabolism that, if sustained on a regular basis, could contribute to unhealthy weight gain.

Technical Abstract:
Background: The results of short-term studies in humans suggest that, compared to glucose, acute consumption of fructose leads to increased postprandial energy expenditure (PPEE) and carbohydrate oxidation and decreased postprandial fat oxidation. Objective: To determine the relative effects of these dietary sugars on energy expenditure and substrate utilization following sustained consumption. Design: As part of a double-blinded parallel arm study, older, overweight and obese male and female subjects consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks. Energy expenditure and substrate utilization were assessed using indirect calorimetry at baseline and following 10 weeks of intervention. Results: Consumption of both sugars led to significant decreases in resting and postprandial metabolic rate despite comparable increases in weight. Consumption of fructose, but not glucose, led to significant decreases in postprandial fat oxidation and significant increases in postprandial carbohydrate oxidation and RQ. In subjects consuming fructose, the observed changes in substrate utilization were correlated with increases in de novo lipogenesis (DNL) that were reported previously. In addition, the observed decreases in postprandial fat oxidation were correlated with previously reported increases in intra-abdominal fat area. Conclusions: These findings suggest that sustained consumption of fructose- and glucose-sweetened beverages leads to a decrease in PPEE that is independent of changes in total body mass, and that consumption of fructose specifically leads to significant changes in postprandial substrate utilization that are associated with increases in hepatic DNL.